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Abstract Background Marfan syndrome (MFS) is a hereditary connective tissue disorder involving multiple systems, including ophthalmologic abnormalities. Most cases are due to heterozygous mutations in the fibrillin‐1 gene (FBN1). Other associated genes include LTBP2, MYH11, MYLK, and SLC2A10. There is significant clinical overlap between MFS and other Marfan‐like disorders. Purpose To expand the mutation spectrum of FBN1 gene and validate the pathogenicity of Marfan‐related genes in patients with MFS and ocular manifestations. Methods We recruited 318 participants (195 cases, 123 controls), including 59 sporadic cases and 88 families. All patients had comprehensive ophthalmic examinations showing ocular features of MFS and met Ghent criteria. Additionally, 754 cases with other eye diseases were recruited. Panel‐based next‐generation sequencing (NGS) screened mutations in 792 genes related to inherited eye diseases. Results We detected 181 mutations with an 84.7% detection rate in sporadic cases and 87.5% in familial cases. The overall detection rate was 86.4%, with FBN1 accounting for 74.8%. In cases without FBN1 mutations, 23 mutations from seven Marfan‐related genes were identified, including four pathogenic or likely pathogenic mutations in LTBP2. The 181 mutations included 165 missenses, 10 splicings, three frameshifts, and three nonsenses. FBN1 accounted for 53.0% of mutations. The most prevalent pathogenic mutation was FBN1 c.4096G>A. Additionally, 94 novel mutations were detected, with 13 de novo mutations in 14 families. Conclusion We expanded the mutation spectrum of the FBN1 gene and provided evidence for the pathogenicity of other Marfan‐related genes. Variants in LTBP2 may contribute to the ocular manifestations in MFS, underscoring its role in phenotypic diversity.

The photonics-assisted millimeter-wave (MMW) communication technology is attractive to facilitate the MMW application in the upcoming B5G and 6G networks. However, its generated MMW signal by optical heterodyne detection usually suffers from serious laser phase noise, which will severely deteriorate the system performance. In this paper, based on a single dual-drive Mach-Zehnder modulator and a single-end photodetector, we first present a simple and spectrally efficient hybrid fiber-wireless double-sideband transmission by employing an overlapping frequency multiplexing scheme. That is, two independent wireless signals with an identical carrier frequency can be simultaneously transmitted in the hybrid fiber-wireless links. To recover the above two overlapped signals, and cancel the concomitant laser phase noise at the same time, a novel digital signal processing method for carrier extraction and signal recovery is further proposed. A proof-of-concept experiment using two independent 3-GBd quadrature phase shift keying (QPSK) signals at W band (92.5 GHz) is performed. After up to 80-km fiber and 3-m wireless transmission, the two QPSK signals can be successfully demodulated, without using the traditional carrier phase estimation algorithm. The proposed scheme not only can double the spectral efficiency of conventional double sideband transmission scheme, but also is immune to its power fading phenomenon induced by chromatic dispersion and robust to the laser phase noise resulting from two free-running lasers in the photonics-assisted MMW communication link.

Abstract Preeclampsia is a multifactorial and heterogeneous complication of pregnancy. Here, we utilize single-cell RNA sequencing to dissect the involvement of circulating immune cells in preeclampsia. Our findings reveal downregulation of immune response in lymphocyte subsets in preeclampsia, such as reduction in natural killer cells and cytotoxic genes expression, and expansion of regulatory T cells. But the activation of naïve T cell and monocyte subsets, as well as increased MHC-II-mediated pathway in antigen-presenting cells were still observed in preeclampsia. Notably, we identified key monocyte subsets in preeclampsia, with significantly increased expression of angiogenesis pathways and pro-inflammatory S100 family genes in VCAN+ monocytes and IFN+ non-classical monocytes. Furthermore, four cell-type-specific machine-learning models have been developed to identify potential diagnostic indicators of preeclampsia. Collectively, our study demonstrates transcriptomic alternations of circulating immune cells and identifies immune components that could be involved in pathophysiology of preeclampsia.

ObjectivesMatrix-assisted laser desorption ionization-time of flight mass spectrometry (MALDI-TOF MS) has emerged as a potent tool for detecting drug resistance in tuberculosis (TB); however, concerns about its reliability have been raised. In this study, we assessed the reliability of MassARRAY (Sequenom, Inc.), which is a MALDI-TOF MS-based method, by comparing it to the well-established GeneXpert assay (Cepheid) as a reference method.MethodsA retrospective study was conducted using laboratory data retrieved from Henan Chest Hospital (Zhengzhou, China). To ensure a rigorous evaluation, we adopted a comprehensive assessment approach by integrating multiple outcomes of the Xpert assay across various specimen types.ResultsAmong the 170 enrolled TB cases, MassARRAY demonstrated significantly higher sensitivity (85.88%, 146 of 170) compared to the Xpert assay (76.62%, 118 of 154) in TB diagnosis (p

With the explosive growth in demand for lithium (Li) resources, the Mufushan area has been a hotspot for Li deposit exploration in China in recent years. Geochemical maps and geochemical anomaly maps are basic maps in the geochemical exploration of mineral resources. A fixed-value method to contour a Li geochemical map is presented here, in which Li concentrations are divided into 19 levels on 18 fixed values, ranging from 5 μg/g (corresponding to the detection limit) to 1858 μg/g (corresponding to the cut-off grade of Li deposit in hard-rock type) and illustrated in six color tones corresponding to Li areas of low background, high background, low anomaly, high anomaly, mineralization in clay-type, and mineralization in hard-rock type. The geochemical map of Li in the Mufushan area using the new fixed-value method indicates that the study area belongs to the high background area, and the known Li deposits are located in the high anomaly areas. In addition, the geochemical anomaly map of the Mufushan area is drawn using the method of seven levels of classification, and indicates that the known Li deposits are all in the anomaly areas, with anomaly levels not lower than the second level. Furthermore, four other areas are recognized for Li resource potential based on the geochemical map and geochemical anomaly map in the Mufushan area.

Changing film thickness to manipulate microstructural properties has been considered as a potential method in practical application. Here, we report that atomic-scale structural properties are regulated by film thickness in an NiCO2O4(NCO)/CuFe2O4(CFO) bilayer heterostructure prepared on (001)-MgAl2O4 (MAO) substrate by means of aberration-corrected scanning transmission electron microscopy (STEM). The misfit dislocations at the NCO/CFO interface and antiphase boundaries (APBs) bound to dislocations within the films are both found in NCO (40 nm)/CFO (40 nm)/MAO heterostructures, contributing to the relaxation of mismatch lattice strain. In addition, the non-overlapping a/4[101]-APB is found and the structural transformation of this kind of APB is resolved at the atomic scale. In contrast, only the interfacial dislocations form at the interface without the formation of APBs within the films in NCO (10 nm)/CFO (40 nm)/MAO heterostructures. Our results provide evidence that the formation of microstructural defects can be regulated by changing film thickness to tune the magnetic properties of epitaxial bilayer spinel oxide films.

Abstract. Background:. Although overnight fasting is recommended prior to endoscopic retrograde cholangiopancreatography (ERCP), the benefits and safety of high-carbohydrate fluid diet (CFD) intake 2 h before ERCP remain unclear. This study aimed to analyze whether high-CFD intake 2 h before ERCP can be safe and accelerate patients' recovery. Methods:. This prospective, multicenter, randomized controlled trial involved 15 tertiary ERCP centers. A total of 1330 patients were randomized into CFD group (n = 665) and fasting group (n = 665). The CFD group received 400 mL of maltodextrin orally 2 h before ERCP, while the control group abstained from food/water overnight (>6 h) before ERCP. All ERCP procedures were performed using deep sedation with intravenous propofol. The investigators were blinded but not the patients. The primary outcomes included postoperative fatigue and abdominal pain score, and the secondary outcomes included complications and changes in metabolic indicators. The outcomes were analyzed according to a modified intention-to-treat principle. Results:. The post-ERCP fatigue scores were significantly lower at 4 h (4.1 ± 2.6 vs. 4.8 ± 2.8, t = 4.23, P

Chaya County in eastern Xizang was selected as the research area for the susceptibility assessment of geological disasters. Seven evaluation indexes, including elevation, slope grade, slope form, slope direction, slope structure, stratum, and distance from fault, were selected to construct an evaluation model of geological disaster susceptibility using the evidence weight method. Using the annual maximum daily rainfall under four rainfall frequencies (10%, 5%, 2%, 1%) as the dynamic inducing factor and building population and transportation facilities as the hazard bearing body, the dynamic risk of geological hazards in the town was evaluated. The results show that except for the small slopes on both sides of the county town, which were mainly high-risk and extremely high-risk areas, other areas in the research area were mainly medium and low-risk areas. As the frequency of rainfall decreased, the areas of high-risk and extremely high-risk areas increased by a maximum of 5.34% and 0.07%, respectively, while the areas of low-risk and medium-risk areas changed by a maximum of 28.33% and 23.32%, respectively. Based on the risk assessment results, a method for controlling the source of geological hazard risk considering different rainfall frequencies was proposed. Specifically, for the extremely high-risk areas under the four rainfall frequencies of 10%, 5%, 2% and 1%, it is recommended to adopt engineering management, engineering management/professional monitoring, professional monitoring, and professional monitoring/combination of mass monitoring and professional monitoring. For the high-risk and medium-risk areas under a 1% rainfall frequency, the recommended risk control measures were the combination of mass monitoring and professional monitoring, and the combination of mass supervision and mass prevention.The risk management and control system accounted for the dynamic risks of slopes under different rainfall frequencies, which would enhance the management and control of geological hazard risks in mountainous urban areas in a refined manner.

α-Ketoglutarate (AKG), a crucial intermediate in the tricarboxylic acid cycle, has been demonstrated to mitigate hyperlipidemia-induced dyslipidemia and endothelial damage. While hyperlipidemia stands as a major trigger for non-alcoholic fatty liver disease, the protection of AKG on hyperlipidemia-induced hepatic metabolic disorders remains underexplored. This study aims to investigate the potential protective effects and mechanisms of AKG against hepatic lipid metabolic disorders caused by acute hyperlipidemia. Our observations indicate that AKG effectively alleviates hepatic lipid accumulation, mitochondrial dysfunction, and loss of redox homeostasis in P407-induced hyperlipidemia mice, as well as in palmitate-injured HepG2 cells and primary hepatocytes. Mechanistic insights reveal that the preventive effects are mediated by activating the AMPK-PGC-1α/Nrf2 pathway. In conclusion, our findings shed light on the role and mechanism of AKG in ameliorating abnormal lipid metabolic disorders in hyperlipidemia-induced fatty liver, suggesting that AKG, an endogenous mitochondrial nutrient, holds promising potential for addressing hyperlipidemia-induced fatty liver conditions.

Sleep deprivation (SD) triggers mitochondrial dysfunction and neural inflammation, leading to cognitive impairment and mental issues. However, the mechanism involving mitochondrial dysfunction and neural inflammation still remains unclear. Here, we report that SD rats exhibited multiple behavioral disorders, brain oxidative stress, and robust brain mitochondrial DNA (mtDNA) oxidation. In particular, SD activated microglia and microglial mtDNA efflux to the cytosol and provoked brain pro-inflammatory cytokines. We observed that the mtDNA efflux and pro-inflammatory cytokines significantly reduced with the suppression of the mtDNA oxidation. With the treatment of a novel mitochondrial nutrient, hydroxytyrosol butyrate (HTHB), the SD-induced behavioral disorders were significantly ameliorated while mtDNA oxidation, mtDNA release, and NF-κB activation were remarkably alleviated in both the rat brain and the N9 microglial cell line. Together, these results indicate that microglial mtDNA oxidation and the resultant release induced by SD mediate neural inflammation and HTHB prevents mtDNA oxidation and efflux, providing a potential treatment for SD-induced mental issues.

Over the past few years, many scholars began to study averaging principles for fractional stochastic differential equations since they can provide an approximate analytical method to reduce such systems. However, in the most previous studies, there is a misunderstanding of the standard form of fractional stochastic differential equations, which consequently causes the wrong estimation of the convergence rate. In this note, we take fractional stochastic differential equations with Lévy noise as an example to clarify these two issues. The corrections herein have no effect on the main proofs except the two points mentioned above. The innovation of this paper lies in three aspects: (i) the standard form of the fractional stochastic differential equations is derived under natural time scale; (ii) it is first proved that the convergence interval and rate are related to the fractional order; and (iii) the presented results contain and improve some well known research achievements.

The shear behavior of the Bolt-Grout interface has a significant effect on the stability of a bolting system. In this paper, a series of shear tests were conducted on Bolt-Grout interfaces, and the effects of rib spacing, rib angles, and normal stress on the shear characteristics and failure modes of the Bolt-Grout interface were investigated. The results showed that the shear strength varied nonlinearly with an increase in rib spacing and angle, and also that it increased linearly with an increase in normal stress. With smaller rib spacings, the effect of rib spacing on peak shear strength was more apparent. The failure modes of the interface can be categorized as shear-slip failure, shear-break failure, and composite failure. The proportion of shear-slip failure and shear-break failure mainly depends on the rib spacing, rib face angle and normal stress.

Psoriasis is one of several chronic inflammatory skin diseases with a high rate of recurrence, and its pathogenesis remains unclear. Nicotinamide mononucleotide (NMN), as an important precursor of nicotinamide adenine dinucleotide (NAD+), has been reported to be a promising agent in treating various diseases, its positive effects including those induced via its anti-inflammatory and antioxidant properties. For this reason, we have aimed to explore the possible role of NMN in the treatment of psoriasis. Psoriasis models were constructed with imiquimod (IMQ) stimulation for 5 days in vivo and with M5 treatment in keratinocyte cell lines in vitro. NMN treatment during the IMQ application period markedly attenuated excess epidermal proliferation, splenomegaly, and inflammatory responses. According to GEO databases, Sirtuin1 (SIRT1) levels significantly decreased in psoriasis patients’ lesion tissues; this was also the case in the IMQ-treated mice, while NMN treatment reversed the SIRT1 decline in the mouse model. Moreover, NMN supplementation also improved the prognoses of the mice after IMQ stimulation, compared to the untreated group with elevated SIRT1 levels. In HEKa and HaCaT cells, the co-culturing of NMN and M5 significantly decreased the expression levels of proinflammation factors, the phosphorylation of NF-κB, stimulator of interferon genes (STING) levels, and reactive oxygen species levels. NMN treatment also recovered the decrease in mitochondrial membrane potential and respiration ability and reduced mtDNA in the cytoplasm, leading to the inhibition of autoimmune inflammation. The knockdown of SIRT1 in vitro eliminated the protective and therapeutic effects of NMN against M5. To conclude, our results indicate that NMN protects against IMQ-induced psoriatic inflammation, oxidative stress, and mitochondrial dysfunction by activating the SIRT1 pathway.

Auricularia auricula-judae (AAJ) has been cultivated for food in China for centuries, and is also used as a folk medicine for the regulation of glucose and lipid metabolism. However, there are few studies on the effects of different processing technologies on the therapeutic efficacy of AAJ to date. This study investigated the effectiveness of the AAJ made by using superfine grinding and enzymatic pre-digestion technologies, respectively, in a high-fat diet obese rat model. It was found that oral administrations of two AAJ products significantly alleviated dyslipidemia by decreasing serum lipid levels and restoring liver functions. AAJ products made by using pre-digestion technology have appreciable potential to ameliorate lipid metabolic disorders over other products, possibly due to the higher levels of dietary fiber, crude polysaccharides, and total flavonoids released from AAJ during processing. By analysis of transcriptome sequencing and protein expression, it was clear that starch and sucrose metabolism and glycerolipid metabolism-related factors involved in fatty acid synthesis and metabolism in the liver of obese rats were significantly improved. This study gives further evidence that AAJ significantly ameliorates the progression of glucose and lipid metabolism in obese rats. Moreover, this study demonstrated for the first time that the pre-digestion method may be a better and more efficient processing approach for the improvement of AAJ bioavailability.

Gold precipitation in hydrothermal systems is traditionally attributed to supersaturation of gold due to decreasing gold complex stability triggered by changes in physicochemical conditions of the ore fluid. However, ultrahigh-grade gold veins in orogenic (shear zone related) gold deposits can contain kilograms per tonne of gold or more, in marked contrast to the typically very low gold concentrations (tens of parts per billion) in fluid. The gold mineral assemblage is commonly restricted to native gold and/or Au-(Ag)-tellurides and occurs in micro-fractures of sheared quartz veins. Textural and compositional characterization of such assemblages, coupled with hydrothermal diamond anvil cell experiments and heating-freezing experiments, provides evidence for an alternative ultrahigh-grade gold enrichment mechanism via growth of polymetallic melt droplets induced by quartz fracturing. We propose that polymetallic melt droplets of Au-Ag-Te-Bi-rich composition form through adsorption-reduction of metal complexes on fractured quartz surfaces, where surface silanol groups and hydrogen serve as reductants. The melt droplets subsequently grow by catalyzing reduction of metal complexes and absorbing metals from fluids percolating in the fractured quartz network. The mobile and reactive polymetallic melt droplets can repeatedly react with the fluid on protracted quartz fracturing and efficiently continue to scavenge gold from multiple pulses of gold-undersaturated ore fluids. [ABSTRACT FROM AUTHOR]

Nontuberculous mycobacteria (NTM) is a large group of mycobacteria other than the Mycobacterium tuberculosis complex and Mycobacterium leprae. Epidemiological investigations have found that the incidence of NTM infections is increasing in China, and it is naturally resistant to many antibiotics. Therefore, studies of NTM species in clinical isolates are useful for understanding the epidemiology of NTM infections. The present study aimed to investigate the incidence of NTM infections and types of NTM species. Of the 420 samples collected, 285 were positive for M. tuberculosis , 62 samples were negative, and the remaining 73 samples contained NTM, including 35 (8.3%) only NTM and 38 (9%) mixed ( M. tuberculosis and NTM). The most prevalent NTM species were Mycobacterium intracellulare (30.1%), followed by Mycobacterium abscessus (15%) and M. triviale (12%). M. gordonae infection was detected in 9.5% of total NTM-positive cases. Moreover, this study reports the presence of Mycobacterium nonchromogenicum infection and a high prevalence of M. triviale for the first time in Henan. M. intracellulare is the most prevalent, accompanied by some emerging NTM species, including M. nonchromogenicum and a high prevalence of M. triviale in Henan Province. Monitoring NTM transmission and epidemiology could enhance mycobacteriosis management in future.